Refractory and relapsed hairy-cell leukemia (HCL): casting light on promising experimental drugs in clinical trials

ABSTRACT

Introduction

Hairy cell leukemia (HCL) is a rare subtype of indolent lymphoid leukemia originating from a mature B lymphocyte. The standard first-line treatment for classic HCL, and HCL variant (HCLv), consists of purine nucleoside analogs (PNA), with or without rituximab. However, almost half of patients relapse and require subsequent therapy.

Areas covered

This article summarizes recent achievements in the treatment of relapsed and refractory HCL. A literature search was conducted of the PubMed and MEDLINE database for articles in English. Publications from 2010 through January 2023 were scrutinized. The search terms used were hairy cell leukemia in conjunction with BRAF inhibitors, Bruton’s tyrosine kinase (BTK) inhibitors, CD20 monoclonal antibodies, relapsed, refractory and variant.

The growing understanding of HCL biology has allowed the design of several new, chemotherapy-free targeted drugs which have demonstrated encouraging efficacy in early clinical trials.

Expert opinion

Novel drugs will soon be available to assist standard therapy for HCL and HCLv among patients with suboptimal results following PNA treatment. In particular, the BRAF inhibitors vemurafenib and dabrafenib, with or without rituximab, have revolutionized treatment of patients with relapsed or refractory disease

KEYWORDS:

• BRAF
• ibrutinib
• moxetumomab pasudotox
• dabrafenib
• hairy cell leukemia
• novel drugs
• trametinib
• variant
• vemurafenib

Article highlights

• Recently, novel drugs or therapies are being investigated in relapsed/refractory HCL patients.

• Rituximab, an anti-CD20 monoclonal antibody, is active in HCL when used alone or in combination with other agents.

• The anti-CD22 immunotoxin moxetumomab pasudotox is effective for patients with relapsed/refractory HCL but is no longer available for commercial reasons.

• The oral BRAFV600 inhibitors, vemurafenib and dabrafenib, demonstrate strong activity in cases of multiple relapsed/refractory HCL.

• Combining BRAF inhibitors with anti-CD20 monoclonal antibodies or MEK inhibitors is promising strategy for treatment of relapsed/refractory HCL

• The BTK inhibitor ibrutinib has demonstrated therapeutic activity in relapsed HCL and HCL variant

Acknowledgments

We thank Edward Lowczowski from the Medical University of Lodz, Poland for editorial assistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

T Robak and P Robak wrote and reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This work was supported in part by the grants from the Medical University of Lodz, Poland (No. 503/1-093-01/503-11-004 and 503/1093-1/503-11-003).